Rabies is a major threat to public health, causing between 50,000 and 60,000 human deaths each year (World Health Organization, April 2003). Humans get infected with the rabies virus mostly through bites from rabid domestic and wildlife animals. In developing countries, dogs are responsible for about 94% of human rabies deaths. Dog rabies is still epizootic in most countries of Africa, Asia and South America, and in these countries dogs are responsible for most human deaths from the disease. Controlling rabies virus infection in domestic and wildlife animals, therefore, not only reduces the mortality in these animals but also reduces the risks of human exposure.
The rabies virus is transmitted through broken skin by the bite or scratch of an infected animal. Exposure to rabies virus results in its penetration of peripheral, unmyelinated nerve endings, followed by spreading through retrograde axonal transport, replication occurring exclusively in the neurons, and finally arrival in the central nervous system (CNS). Infection of the CNS causes cellular dysfunction and death (Rupprecht and Dietzschold, Lab Invest. 57:603, 1987). Since rabies virus spreads directly from cell to cell, it largely evades immune recognition (Clark and Prabhakar, Rabies, In: Olson et al., eds., “Comparative Pathology of Viral Disease,” 2:165, Boca Raton, Fla., CRC Press, 1985).
Population control of dogs with outdated methods of capture, restraint and euthanasia are inhumane and not acceptable to the public. Canine rabies prevention and control, and appropriate population management of free-ranging dogs are paramount for eventual disease elimination. Various approaches have been proposed to interrupt canine reproductive cycles, including surgical spay/neuter of animals, chemical sterilization, and immunocontraception. For example, gonadotropin releasing hormone (GnRH) has been considered as one approach as an immunocontraceptive peptide for dogs. However, studies to date have shown that GnRH needs to be synthesized and conjugated with a carrier protein (or adjuvant) to be immunogenic. Necessary scale-up of production may become problematic to meet the regulatory and economic demands for modern vaccine supply. Thus, it is desirable to construct a vaccine that can induce appropriate dual immunological responses against both rabies virus and immunocontraceptive targets, after a single administration in animals.
Moreover, over the past 30 years, immunocontraceptive studies have not generated a single commercial product. Technical limitations are one of the main factors. Therefore, there is a long unfelt need for a novel rabies virus vaccine, engineered with the ability to express a suitable immunocontraceptive gene. This type of vaccine would be an ideal candidate for both rabies prevention and population control of wild and domestic animals, including dogs.